Lysosomal and network alterations in human mucopolysaccharidosis type VII iPSC-derived neural cells

Mucopolysaccharidosis type VII (MPS VII) is a lysosomal storage disease caused by deficient β-glucuronidase (β-gluc) activity. Significantly reduced β-gluc activity leads to accumulation of glycosaminoglycans (GAGs) in many tissues, including the brain. Numerous combinations of mutations in GUSB (the gene that codes for β-gluc) cause a range of neurological features that make disease prognosis and treatment challenging. Currently, there is little understanding of the molecular basis for MPS VII brain anomalies. To identify a neuronal phenotype that could be used to complement genetic analyses, we generated two iPSC clones derived from skin fibroblasts of an MPS VII patient. We found that MPS VII neurons exhibited reduced β-gluc activity and showed previously established disease-associated phenotypes, including GAGs accumulation, expanded endocytic compartments, accumulation of lipofuscin granules, more autophagosomes, and altered lysosome function. Addition of recombinant β-gluc to MPS VII neurons, which mimics enzyme replacement therapy, restored disease-associated phenotypes to levels similar to the healthy control. MPS VII neural cells cultured as 3D neurospheroids showed upregulated GFAP gene expression, which was associated with astrocyte reactivity, and downregulation of GABAergic neuron markers. Spontaneous calcium imaging analysis of MPS VII neurospheroids showed reduced neuronal activity and altered network connectivity in patient-derived neurospheroids compared to a healthy control. These results demonstrate the interplay between reduced β-gluc activity, GAG accumulation and alterations in neuronal activity, and provide a human experimental model for elucidating the bases of MPS VII-associated cognitive defects

Pratique du peau à peau et de la mise au sein précoce entre césarienne et voie basse : étude constituée de deux volets au sein d'une maternité de niveau III dans la région Auvergne-Rhône-Alpes

Introduction : C-section (CS) is more commun in developed countries. Women have poor knowledge about its organization and its post partum. The WHO recommends a first skin to skin (STS) contact and early breastfeeding in the first hour after birth. However they are differences in practice between CS and vaginal delivery (VD). This study looked at the different practices of breastfeeding and STS in the post partum.Study design : An observational descriptive study was conducted from September 2016 to January 2017. 147 patients were enrolled at the type-3 maternity hospital in the Auvergne-Rhône-Alpes region. 120 questionnaires were collected and interpreted. A qualitative study was also conducted through interviews with obstetric unit professionals.Results : For STS and breastfeeding, the difference between CS and VD is statistically significant. Concerning breastfeeding and STS brakes in post-surgery care room, it was highlighted by the professionals, an intense activity of the service and logistical problems.Discussion : Patients were unable to explain why STS and early breastfeeding were not done. A contradiction exists between the two studies. In fact, the professionals interviewed ensure that they practice all breastfeeding. But few patients, who had a CS, say they had it. An improvement of the practices by the updating of the material is recommended.Introduction : La césarienne est répandue dans les pays industrialisés. Les femmes sont peu informées sur son déroulement et ses suites de couche. L’OMS recommande un premier contact en peau à peau (PAP) et une première mise au sein (MAS) effectuée dans la première heure suivant la naissance. Or il existe des différences de pratiques entre les césariennes et les voies basses (VB). Cette étude s’est donc intéressée aux différences de pratiques de l’allaitement maternel (AM) et du PAP dans le post-partum immédiat.Population et méthode : Une étude observationnelle descriptive a été réalisée de septembre 2016 à janvier 2017. 147 patientes ont été recrutées au sein d’une maternité de niveau III en région Auvergne-Rhône-Alpes et 120 questionnaires ont été recueillis et interprétés. Une étude qualitative a également été réalisée au moyen d’entretiens auprès de professionnels du bloc obstétrical.Résultats : Pour le PAP et la MAS précoce, la différence entre les VB et les césariennes est statistiquement significatif. Concernant les freins au PAP et MAS en SSPI, il a été mis en évidence par les professionnels : une activité intense du service et des problèmes logistiques.Discussion : Les causes de non pratiques du PAP et des MAS ont été peu explorées auprès des patientes. Une controverse existe entre les deux études : les professionnels interrogés assurent pratiquer toutes les mises au sein or peu de patientes césarisées déclarent l’avoir eu. Une amélioration des pratiques par notamment la mise à jour du matériel est préconisée

ETUDE CHEZ LE RAT DE L'INFLUENCE DU MAGNESIUM SUR LA SENSIBILITE AUX STIMULI NOCICEPTIFS (APPROCHES COMPORTEMENTALES ET PHARMACOALOGIQUES (DOCTORAT : NEUROPHARMACOLOGIE))

CLERMONT FD-BCIU-Santé (631132104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Esthétique en prothèse amovible partielle

De nombreuses études épidémiologiques, incluant l'implantologie, montrent qu'il existe encore beaucoup de patients édentés qui, pour diverses raisons, restent candidats à la prothèse amovible partielle (PAP). La PAP représente donc toujours une thérapeutique d'actualité et il est du devoir du praticien de continuer à la perfectionner pour répondre aux exigences esthétiques et fonctionnelles du patient. La motivation esthétique est sans aucun doute la plus difficile à appréhender: si la réhabilitation des fonctions est invariable dans le temps, celle de l'aspect esthétique fluctue au gré des époques, des milieux socio-culturels ou même des individus. Au cours de ce travail, nous allons donc établir comment obtenir une PAP conforme aux critères esthétiques définis au préalable avec le patient. Cette intégration intervient à chaque étape du traitement, pré, per et post-prothétique, et concerne aussi bien l'aménagement du lit prothétique, la dissimulation des éléments du châssis et l'assimilation des éléments postiches.NANTES-BU Médecine pharmacie (441092101) / SudocPARIS-BIUM (751062103) / SudocLILLE2-UFR Odontologie (593502202) / SudocNANTES-Bib.Odontologie (441092219) / SudocSudocFranceF

Three-dimensional vertebral wedging in mild and moderate adolescent idiopathic scoliosis.

Vertebral wedging is associated with spinal deformity progression in adolescent idiopathic scoliosis. Reporting frontal and sagittal wedging separately could be misleading since these are projected values of a single three-dimensional deformation of the vertebral body. The objectives of this study were to determine if three-dimensional vertebral body wedging is present in mild scoliosis and if there are a preferential vertebral level, position and plane of deformation with increasing scoliotic severity.Twenty-seven adolescent idiopathic scoliotic girls with mild to moderate Cobb angles (10° to 50°) participated in this study. All subjects had at least one set of bi-planar radiographs taken with the EOS® X-ray imaging system prior to any treatment. Subjects were divided into two groups, separating the mild (under 20°) from the moderate (20° and over) spinal scoliotic deformities. Wedging was calculated in three different geometric planes with respect to the smallest edge of the vertebral body.Factorial analyses of variance revealed a main effect for the scoliosis severity but no main effect of vertebral Levels (apex and each of the three vertebrae above and below it) (F = 1.78, p = 0.101). Main effects of vertebral Positions (apex and above or below it) (F = 4.20, p = 0.015) and wedging Planes (F = 34.36, p<0.001) were also noted. Post-hoc analysis demonstrated a greater wedging in the inferior group of vertebrae (3.6°) than the superior group (2.9°, p = 0.019) and a significantly greater wedging (p≤0.03) along the sagittal plane (4.3°).Vertebral wedging was present in mild scoliosis and increased as the scoliosis progressed. The greater wedging of the inferior group of vertebrae could be important in estimating the most distal vertebral segment to be restrained by bracing or to be fused in surgery. Largest vertebral body wedging values obtained in the sagittal plane support the claim that scoliosis could be initiated through a hypokyphosis

Thoracic and lumbar vertebrae digitization.

<p>Firstly a bony landmark was identified on the postero-anterior radiograph. A horizontal line drawn from this point was projected on the lateral radiograph. The intersection between the horizontal line and the edge of the vertebral body ensured that the same bony landmark was identified in each pair of radiographs.</p

Combined effect of three superior and three inferior vertebrae wedging compared to the apex vertebra.

<p>Circles represent the average wedging and bars represent the 95% confidence interval. The mild scoliosis group is in blue and the moderate scoliosis group is in green.</p

Mean age and Cobb angle values with standard deviations, and Cobb angle range given for the mild and moderately severe scoliosis groups.

<p>Mean age and Cobb angle values with standard deviations, and Cobb angle range given for the mild and moderately severe scoliosis groups.</p

Extent of wedging at the apex and at each of three vertebrae above and below.

<p>Circles represent the average wedging and bars represent the 95% confidence interval. The mild scoliosis group is in blue and the moderate scoliosis group is in green.</p

Vertebral wedging values obtained for the frontal, sagittal and diagonal edges.

<p>Circles represent the average wedging and bars represent the 95% confidence interval. The mild scoliosis group is in blue and the moderate scoliosis group is in green.</p